Haemolytic anaemia

Question 1

What are some causes of intravascular haemolysis?

Answer 1

Mismatched blood transfusion, G6PD deficiency, RBC fragmentation (metallic valves, TTP, DIC, HUC), cold autoimmune haemolytic anaemia.
Osmotic lysis (occurs with hypotonic fluid as fluid moves into RBCs causing them to burst)
Presents with low haptoglobin (which is what binds free Hb), as it becomes saturated haemoglobin will then bind to albumin forming methaemalbumin

Question 2

What are some causes of extravascular haemolysis?

Answer 2

Haemoglobinopathies,
Hereditary spheocytosis,
Haemolytic disease of the newborn,
Warm autoimmune haemolytic anaemia

Question 3

What are hereditary causes of haemoltic anaemia?

Answer 3

Membrane: hereditary spherocytosis,
Metabolic: G6PD deficiency,
Haemoglobinopathies

Question 4

What are immune acquired causes of haemolyic anaemia

Answer 4

Coombs positive!
Warm/cold AIHA,
Alloimmune (HDN),
Drug induced haemolyic anaemia

Question 5

What are non-immune acquired haemolytic anaemia causes

Answer 5

Coombs negative - no antibodies!
Microangiopathic haemolytic anaemia (TTP, HUS, DIC, Malignancy, pre-eclampsia)
Prosthetic heart valves,
Paroxysmal noctunral haemoglobinuria,
Malaria,
Dapsone,
Zieve syndrome

Question 6

What is Zieve syndrome

Answer 6

Coombs negative haemolyisis, cholestatic jaundice and transient hyperlipidaemia associated with heavy alcohol use.

Question 7

What are the features of haemolytic anaemia?

Answer 7

Anaemia,
Jaundice,
Splenomegaly,
Raised LDH (enzyme found in RBCs), reticulocytes, low haptoglobin and high bilirubin

Question 8

What are the investigations for haemolytic anaemia?

Answer 8

FBC: normocytic anaemia
Blood film: Schistocytes (fragments of RBCs)
Direct coombs test: Positive in autoimmune haemolytic anaemia

Question 9

What are the features of hereditary spherocytosis?

Answer 9

Autosomal dominant condition causes fragile, sphere shaped RBCs which break down easily passing through the spleen.
Presents with anaemia, jaundice, gallstones and splenomegaly

Question 10

What is a complication in hereditary spherocytosis and how does it present?

Answer 10

Aplastic crisis due to parovovirus. Presents with raised MCHC, raised reticulocyte could and spherocytosis.
Investigation - EMA Test

Question 11

WHat is the treatment for hereditary spherocytosis?

Answer 11

Folate supplement, blood transfusion, splenectomy and cholecystectomy if persistent gallstones

Question 12

What is another RBC membrane defect which can cause haemolysis?

Answer 12

Hereditary elliptocytosis

Question 13

What are pathophysiology of G6PD deficiency?

Answer 13

X-linked recessive defect in glucose 6 phosphate dehydrogenase (an enzyme which protects cells from oxidative damage). This leads to accumulation of reactive oxygen species causing damage to cell membrane and eventual haemolysis

Question 14

What are some triggers of haemolytic episodes in G6PD def?

Answer 14

Meds: Sulphonamides eg, sulfamethoxazole. Antimalarials, aspirin, NSAID, Dapsone.
Infections: Viral or bacterial
Fava beans (broad beans),
Chemicals,
Mental or physical stress,
Tonic water,
Soy products,
Vitamin K analogues

Question 15

What are the features and investigations for autoimmune haemolytic anaemia

Answer 15

General features - anaemia, reticulocytosis, low haptoglobin, raised LDH and bilirubin, spherocytes and reticulocytes
Investigations - Positive direct coombs test

Question 16

Describe features of warm haemolytic anaemia

Answer 16

Most common type. Caused by IgG antibodies.
Causes: Idiopathic, autoimmune disease (SLE), neoplastic (lymphoma, CLL), drugs eg methyldopa

Question 17

Describe features of cold haemolytic anaemia?

Answer 17

Caused by IgM and can present with raunauds and acrocyanosis.
Causes: Neoplastic (lymphoma) or infections (mycoplasma or EBV)

Question 18

Describe a direct coombs test?

Answer 18

Anti-human immunoglobulin is used to react with antibodies on the red blood cell surface. If positive then it indicates AIHA and HDN.

Question 19

Describe an indirect coombs test

Answer 19

Patients plasma is mixed with donor blood. Antihuman immunoglobulin is then added to detect the presence of RBC antibodies

Question 20

Whats the treatment for autoimmune haemolytic anaemia?

Answer 20

Cold (IgM) - Self-limiting mycoplasma infection and keep patient warm.

Warm (IgG) - Stop any drugs then give steroids, immunosuppression and splenectomy

Question 21

Describe features of pyruvate kinase deficiency anaemia?

Answer 21

Pyruvate kinase def results in ATP depletion and then haemolysis. It presents with chronic, extravascular haemolytic anaemia

Question 22

Describe features of paroxysmal nocturnal haemoglobinuria

Answer 22

It is caused by an acquired mutation in haematopoietic stem cells resulting in loss of surface protein which inhibits complement activation. Without this protein, RBCs are destroyes.
Presents with red urine in morning, anaemia, thrombosis and smooth muscle dystonia (oesophageal spasm or erectile dyfunction)

Question 23

What is the management of Paroxysmal nocturnal haemoglobinuria

Answer 23

Eculizumab or bone marrow transplant

Question 24

What is microangiopathic haemolytic anaemia?

Answer 24

Restruciton of RBCs as they travel through ciruclation. Most commonly caused by abnormal clotting which results in small thombi partially obstructing vessels and causing destruction of RBCs on their way past.
Schistocytes are key blood film finding

Question 25

What are some causes of microangiopathic haemolytic anaemia?

Answer 25

Haemolytic uraemic syndrome,
Disseminated intravascular coagulation,
Thrombotic thombocytopenic purpura,
Systemic lupus erythematosus,
Cancer